Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers.
BACKGROUND
Triple-negative breast cancer (estrogen receptor-, progesterone receptor-, and HER2-negative) (TNBC) is a high risk breast cancer that lacks specific therapy targeting these proteins.


METHODS
We studied 969 consecutive Japanese patients diagnosed with invasive breast cancer from January 1981 to December 2003, and selected TNBCs based on the immunohistochemical data. Analyses of epidermal growth factor receptor (EGFR) gene mutations and amplification, and BRCA1 mRNA expression were performed on these samples using TaqMan PCR assays. The prognostic significance of TNBCs was also explored. Median follow-up was 8.3 years.


RESULTS
A total of 110 (11.3%) patients had TNBCs in our series. Genotyping of the EGFR gene was performed to detect 14 known EGFR mutations, but none was identified. However, EGFR gene copy number was increased in 21% of TNBCs, while only 2% of ER- and PgR-positive, HER2-negative tumors showed slightly increased EGFR gene copy numbers. Thirty-one percent of TNBCs stained positive for EGFR protein by immunohistochemistry. BRCA1 mRNA expression was also decreased in TNBCs compared with controls. Triple negativity was significantly associated with grade 3 tumors, TP53 protein accumulation, and high Ki67 expression. TNBC patients had shorter disease-free survival than non-TNBC in node-negative breast cancers.


CONCLUSIONS
TNBCs have an aggressive clinical course, and EGFR and BRCA1 might be candidate therapeutic targets in this disease.
Toyama
Tatsuya
T
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. toyamat-ncu@umin.ac.jp
Yamashita
Hiroko
H
Kondo
Naoto
N
Okuda
Katsuhiro
K
Takahashi
Satoru
S
Sasaki
Hidefumi
H
Sugiura
Hiroshi
H
Iwase
Hirotaka
H
Fujii
Yoshitaka
Y
D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone